Abstract Precision Interception of Aggressive Prostate Cancer in African American Men Prostatic adenocarcinoma (PCa) is the most frequently diagnosed non-cutaneous malignancy and a leading cause of male cancer death. African American (AA) men die from PCa at a rate more than double that of men of any other race or ethnicity. The causes of this disparity are multifactorial and certainly include unequal access to screening and treatment. Biological differences in the tumors of AA and non-AA men have also been reported that may reflect underlying tumor differences that may also affect prognosis and treatment choice. Our ability to predict and monitor PCa progression and make better treatment choices in AA men is critical to reducing dispari- ties in PCa among AA men. To address these issues, we propose a ?precision interception? approach designed to impede cancer progres- sion at early stages and avoid development of lethal disease in AA PCa cases. Precision interception approach- es use knowledge of molecular signatures and other clinical and epidemiological data to interrupt PCa before it is lethal to the patient. Thus, our proposal will focus on newly diagnosed or recurrent AA PCa patients, with the goal to develop and implement tools that can ?intercept? the development of castrate-resistant or metastatic PCa and death from PCa in AA men. These approaches can thereby reduce PCa-specific disparities in mortality ex- perienced by AA men. We will use the ?Men of African Descent and Carcinoma of the Prostate? (MADCaP) network that has substan- tial resources to address disparities in PCa in AA men. The team assembled here has previously collaborated to develop translational research that is led by established basic and clinical experts who have worked together to develop each concept. The result is a novel inter-disciplinary collaboration with the potential to maximize clinical impact on PCa disparities in AA men. An Administration Core and Biosample and Biomarker Core support the projects. The projects and cores integrate community engagement activities, and the Dana Farber Harvard Can- cer Center SPORE in Prostate Cancer, which itself has substantial resources for preclinical and clinical transla- tion. These resources are complemented by the MADCaP Implementation Network (MADCaP-IN) that includes community and inner city clinics that see a substantial proportion of AA PCa cases. The MADCaP-IN will serve as the centers for research participant accrual as well as centers for the implementation of current and future clinical research. We also include a Dvelopmental Research Pilot program that will focus on implementation and dissemination of our research to have maximal impact on communities. Our proposed translational research should have substantial translational/clinical impact, improve management of and outcomes, and reduce PCa disparities in AA men with PCa.